First-in-human trial of a novel suprachoroidal retinal prosthesis.
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ABSTRACT: Unlabelled
Retinal visual prostheses ("bionic eyes") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration.Trial registration
Clinicaltrials.gov NCT01603576.
SUBMITTER: Ayton LN
PROVIDER: S-EPMC4270734 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
First-in-human trial of a novel suprachoroidal retinal prosthesis.
Ayton Lauren N LN Blamey Peter J PJ Guymer Robyn H RH Luu Chi D CD Nayagam David A X DA Sinclair Nicholas C NC Shivdasani Mohit N MN Yeoh Jonathan J McCombe Mark F MF Briggs Robert J RJ Opie Nicholas L NL Villalobos Joel J Dimitrov Peter N PN Varsamidis Mary M Petoe Matthew A MA McCarthy Chris D CD Walker Janine G JG Barnes Nick N Burkitt Anthony N AN Williams Chris E CE Shepherd Robert K RK Allen Penelope J PJ
PloS one 20141218 12
<h4>Unlabelled</h4>Retinal visual prostheses ("bionic eyes") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients ...[more]
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Project description:PurposeTo report the initial safety and efficacy results of a second-generation (44-channel) suprachoroidal retinal prosthesis at 56 weeks after device activation.MethodsFour subjects, with advanced retinitis pigmentosa and bare-light perception only, enrolled in a phase II trial (NCT03406416). A 44-channel electrode array was implanted in a suprachoroidal pocket. Device stability, efficacy, and adverse events were investigated at 12-week intervals.ResultsAll four subjects were implanted successfully and there were no device-related serious adverse events. Color fundus photography indicated a mild postoperative subretinal hemorrhage in two recipients, which cleared spontaneously within 2 weeks. Optical coherence tomography confirmed device stability and position under the macula. Screen-based localization accuracy was significantly better for all subjects with device on versus device off. Two subjects were significantly better with the device on in a motion discrimination task at 7, 15, and 30°/s and in a spatial discrimination task at 0.033 cycles per degree. All subjects were more accurate with the device on than device off at walking toward a target on a modified door task, localizing and touching tabletop objects, and detecting obstacles in an obstacle avoidance task. A positive effect of the implant on subjects' daily lives was confirmed by an orientation and mobility assessor and subject self-report.ConclusionsThese interim study data demonstrate that the suprachoroidal prosthesis is safe and provides significant improvements in functional vision, activities of daily living, and observer-rated quality of life.Translational relevanceA suprachoroidal prosthesis can provide clinically useful artificial vision while maintaining a safe surgical profile.
| S-EPMC8479573 | biostudies-literature
Project description:PurposeTo investigate oculomotor behavior in response to dynamic stimuli in retinal implant recipients.MethodsThree suprachoroidal retinal implant recipients performed a four-alternative forced-choice motion discrimination task over six sessions longitudinally. Stimuli were a single white bar ("moving bar") or a series of white bars ("moving grating") sweeping left, right, up, or down across a 42″ monitor. Performance was compared with normal video processing and scrambled video processing (randomized image-to-electrode mapping to disrupt spatiotemporal structure). Eye and head movement was monitored throughout the task.ResultsTwo subjects had diminished performance with scrambling, suggesting retinotopic discrimination was used in the normal condition and made smooth pursuit eye movements congruent to the moving bar stimulus direction. These two subjects also made stimulus-related eye movements resembling optokinetic reflex (OKR) for moving grating stimuli, but the movement was incongruent with stimulus direction. The third subject was less adept at the task, appeared primarily reliant on head position cues (head movements were congruent to stimulus direction), and did not exhibit retinotopic discrimination and associated eye movements.ConclusionsOur observation of smooth pursuit indicates residual functionality of cortical direction-selective circuits and implies a more naturalistic perception of motion than expected. A distorted OKR implies improper functionality of retinal direction-selective circuits, possibly due to retinal remodeling or the non-selective nature of the electrical stimulation.Translational relevanceRetinal implant users can make naturalistic eye movements in response to moving stimuli, highlighting the potential for eye tracker feedback to improve perceptual localization and image stabilization in camera-based visual prostheses.
| S-EPMC7757638 | biostudies-literature
Project description:Current surgical techniques for retinal prosthetic implantation require long and complicated surgery, which can increase the risk of complications and adverse outcomes.The suprachoroidal position is known to be an easier location to access surgically, and so this study aimed to develop a surgical procedure for implanting a prototype suprachoroidal retinal prosthesis. The array implantation procedure was developed in 14 enucleated eyes. A full-thickness scleral incision was made parallel to the intermuscular septum and superotemporal to the lateral rectus muscle. A pocket was created in the suprachoroidal space, and the moulded electrode array was inserted. The scleral incision was closed and scleral anchor point sutured. In 9 of the 14 eyes examined, the device insertion was obstructed by the posterior ciliary neurovascular bundle. Subsequently, the position of this neurovascular bundle in 10 eyes was characterized. Implantation and lead routing procedure was then developed in six human cadavers. The array was tunnelled forward from behind the pinna to the orbit. Next, a lateral canthotomy was made. Lead fixation was established by creating an orbitotomy drilled in the frontal process of the zygomatic bone. The lateral rectus muscle was detached, and implantation was carried out. Finally, pinna to lateral canthus measurements were taken on 61 patients in order to determine optimal lead length.These results identified potential anatomical obstructions and informed the anatomical fitting of the suprachoroidal retinal prosthesis.As a result of this work, a straightforward surgical approach for accurate anatomical suprachoroidal array and lead placement was developed for clinical application.
| S-EPMC4233968 | biostudies-literature
Project description:PurposeTo assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.MethodsSeven normally-sighted feline subjects were implanted for 96-143 days with a suprachoroidal electrode array and six were chronically stimulated for 70-105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.ResultsAll subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11-15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.ConclusionsChronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.
| S-EPMC4031073 | biostudies-literature
Project description:PurposeIn a clinical trial (NCT03406416) of a second-generation (44-channel) suprachoroidal retinal prosthesis implanted in subjects with late-stage retinitis pigmentosa (RP), we assessed performance in real-world functional visual tasks and emotional well-being.MethodsThe Functional Low-Vision Observer Rated Assessment (FLORA) and Impact of Vision Impairment-Very Low Vision (IVI-VLV) instruments were administered to four subjects before implantation and after device fitting. The FLORA contains 13 self-reported and 35 observer-reported items ranked for ease of conducting task (impossible-easy, central tendency given as mode). The IVI-VLV instrument quantified the impact of low vision on daily activities and emotional well-being.ResultsThree subjects completed the FLORA for two years after device fitting; the fourth subject ceased participation in the FLORA after fitting for reasons unrelated to the device. For all subjects at each post-fitting visit, the mode ease of task with device ON was better or equal to device OFF. Ease of task improved over the first six months with device ON, then remained stable. Subjects reported improvements in mobility, functional vision, and quality of life with device ON. The IVI-VLV suggested self-assessed vision-related quality of life was not impacted by device implantation or usage.ConclusionsSubjects demonstrated sustained improved ease of task scores with device ON compared to OFF, indicating the device has a positive impact in the real-world setting.Translational relevanceOur suprachoroidal retinal prosthesis shows potential utility in everyday life, by enabling an increased environmental awareness and improving access to sensory information for people with end-stage RP.
| S-EPMC8362639 | biostudies-literature
Project description:PurposeTo report the long-term observations of the electrode-tissue interface and perceptual stability in humans after chronic stimulation with a 44-channel suprachoroidal retinal implant.MethodsFour subjects (S1-4) with end-stage retinitis pigmentosa received the implant unilaterally (NCT03406416). Electrode impedances, electrode-retina distance (measured using optical coherence tomography imaging), and perceptual thresholds were monitored up to 181 weeks after implantation as the subjects used the prosthesis in the laboratory and in daily life. Stimulation charge density was limited to 32 µC/cm2 per phase.ResultsElectrode impedances were stable longitudinally. The electrode-retina distances increased after surgery and then stabilized, and were well-described by an asymptotic exponential model. The stabilization of electrode-retina distances was variable between subjects, stabilizing after 45 weeks for S1, 63 weeks for S2, and 24 weeks for S3 (linear regression; Pgradient > 0.05). For S4, a statistically significant increase in electrode-retina distance persisted (P < 0.05), but by the study end point the rate of increase was clinically insignificant (exponential model: 0.33 µm/wk). Perceptual electrical thresholds were stable in one subject, decreased over time in two subjects (linear model; P < 0.05), and increased slightly in one subject but remained within the predefined charge limits (P = 0.02).ConclusionsChronic stimulation with the suprachoroidal retinal prosthesis over 3 years resulted in stable impedances, small individual changes in perceptual electrical thresholds, and no clinically significant increase in electrode-retina distances after a period of settling after surgery.Translational relevanceChronic stimulation with the 44-channel suprachoroidal retinal implant with a charge density of up to 32 µC/cm2 per phase is suitable for long-term use in humans.
| S-EPMC9202334 | biostudies-literature
Project description:This paper presents a novel sensing configuration for retinal physiology analysis, using two microelectrode arrays (MEAs). In order to investigate an optimized stimulation protocol for a sub-retinal prosthesis, retinal photoreceptor cells are stimulated, and the response of retinal ganglion cells is recorded in an in vitro environment. For photoreceptor cell stimulation, a polyimide-substrate MEA is developed, using the microelectromechanical systems (MEMS) technology. For ganglion cell response recording, a conventional glass-substrate MEA is utilized. This new sensing configuration is used to record the response of retinal ganglion cells with respect to three different stimulation methods (monopolar, bipolar, and dual-monopolar stimulation methods). Results show that the geometrical relation between the stimulation microelectrode locations and the response locations seems very low. The threshold charges of the bipolar stimulation and the monopolar stimulation are in the range of 10~20 nC. The threshold charge of the dual-monopolar stimulation is not obvious. These results provide useful guidelines for developing a sub-retinal prosthesis.
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Project description:PurposeThis study was conducted to investigate the feasibility of a newly developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in dogs and to examine its biocompatibility and stability over a 4-month period.MethodsThree types of STS dual arrays were designed and tested. The STS dual-array was implanted into a scleral pocket of the left eye of six healthy beagle dogs. Ophthalmic examinations, fundus photography, fluorescein angiography (FA), electroretinography (ERG), and functional testing of this system were conducted postoperatively. The dogs were euthanatized at the end of the experiment, and their eyes were enucleated and histologically examined.ResultsAll prostheses were successfully implanted without complications, and no serious adverse event occurred during the postoperative period. Fundus photographs and FA showed no serious damage in the retina surrounding the arrays. The ERGs recorded from the implanted eyes showed no significant differences from those from control eyes. Histological evaluations demonstrated good preservation of the retina over the array. However, system failure occurred in 50% of the dogs owing to dog-specific habits.ConclusionsImplantation of this prosthesis system in dogs is feasible and can be performed without significant damage to the eye. The biocompatibility and stability of the array were good during the observation period, but the low durability of the system against dogs (not humans) is an issue to be resolved in the future.Translational relevanceThis study suggests that this wide-field dual-array prosthesis might widen the visual field and might be useful for patients with retinitis pigmentosa.
| S-EPMC7961109 | biostudies-literature
Project description:ImportanceIn-office suprachoroidal viscopexy (SCVEXY) is a minimally invasive technique for rhegmatogenous retinal detachment (RRD) repair that can be performed with no incision, no tamponade agent, and no positioning requirements. This technique has the potential to be a step forward in the armamentarium to treat RRDs.ObjectiveTo describe in-office SCVEXY for RRD repair.Design, setting, and participantIn this single-case report with short follow-up, a man in his 50s with pseudophakia and recent visual loss presented to St Michael's Hospital, Unity Health Toronto, with a fovea-off RRD in the right eye, extending from 6 to 10 o'clock, with no visible causative retinal break.ExposureInjection of suprachoroidal sodium hyaluronate, 1%, in the region of the suspected break, using a 30-gauge needle with a custom-made guard that exposed only 1 mm of the needle.Main outcome and measuresAbility to perform in-office SCVEXY and to obtain a visible choroidal indentation.ResultsAfter the procedure, a dome-shaped choroidal convexity was present in the superior temporal area. The patient achieved macular reattachment in less than 24 hours with no postoperative abnormalities, such as outer retinal folds, residual subfoveal fluid, or retinal displacement, with rapid recovery of the outer retinal bands on optical coherence tomography. The optical coherence tomography scans acquired in the area of the choroidal convexity demonstrated the location of the viscoelastic material in the suprachoroidal space. Laser retinopexy was applied in the suspected region of the retinal tear, and the patient was able to resume normal activity immediately after the procedure with no restrictions.Conclusions and relevanceSuprachoroidal viscopexy is feasible as an in-office technique to create a temporary choroidal buckle for RRD repair. It is a minimally invasive procedure with the potential to maximize anatomical outcomes of integrity and postoperative functional outcomes in RRD because its mechanism of action does not require drainage of subretinal fluid or intraocular gas tamponade. Nevertheless, this was a single-case report with short follow-up, which limits the ability to determine the procedure's benefits, potential adverse events, failure rates, and best-case selection. Further work is required to refine the procedure and assess its efficacy and safety.
| S-EPMC10587788 | biostudies-literature
Project description:PurposeVision loss due to retinitis pigmentosa affects an estimated 15 million people worldwide. Through collaboration between Second Sight Medical Products, Inc., and the Doheny Eye Institute, six blind human subjects underwent implantation with epiretinal 4 x 4 electrode arrays designed to directly stimulate the remaining cells of the retina, with the goal of restoring functional vision by applying spatiotemporal patterns of stimulation. To better understand spatiotemporal interactions between electrodes during synchronous and asynchronous stimulation, the authors investigated how percepts changed as a function of pulse timing across the electrodes.MethodsPulse trains (20, 40, 80, and 160 Hz) were presented on groups of electrodes with 800, 1600, or 2400 microm center-to-center separation. Stimulation was either synchronous (pulses were presented simultaneously across electrodes) or asynchronous (pulses were phase shifted). Using a same-different discrimination task, the authors were able to evaluate how the perceptual quality of the stimuli changed as a function of phase shifts across multiple electrodes.ResultsEven after controlling for electric field interactions, subjects could discriminate between spatiotemporal pulse train patterns based on differences of phase across electrodes as small as 3 ms. These findings suggest that the quality of the percept is affected not only by electric field interactions but also by spatiotemporal interactions at the neural level.ConclusionsDuring multielectrode stimulation, interactions between electrodes have a significant influence on the quality of the percept. Understanding how these spatiotemporal interactions at the neural level influence percepts during multielectrode stimulation is fundamental to the successful design of a retinal prosthesis.
| S-EPMC2868442 | biostudies-literature